Cryotherapy for Barrettʼs Esophagus and Early Esophageal Cancer: A Pooled Analysis of Cases from 1999-May 2009

Abstract

Purpose: Endoscopic spray cryotherapy is increasingly recognized to be effective in ablating Barrett's esophagus (BE) and early esophageal cancer (EEC). To summarize the current practice and efficacy of cryotherapy for BE and EEC, we conducted a systematic literature review. Methods: We individually searched the literature (PubMed, EMBase, Web of Science, Cochrane, DDW and ACG meeting abstracts from 1999 to May 2009, bibliographies of selected articles). The search was limited to English publications, pilot studies and clinical trials with human participants. We excluded studies on advanced esophageal cancer, cryotherapy combined with other ablative modalities and studies not reporting complete resolution (CR), defined as no histological evidence of BE or neoplasia after treatment. We used the following search terms: cryotherapy, cryoablation, Barrett's esophagus and esophageal cancer. Data from earlier reports by the same authors and study were pooled with their updated reports. Three independent reviewers determined eligibility for inclusion and extracted data. Results: We identified no randomized clinical trials. Our search yielded 46 papers of which 8 met the inclusion criteria. These were published from 2006 to April 2009 with a total of 222 enrolled patients (mean age 68.5 yrs; 50-87% male). All studies were prospective case series, with cryotherapy as either primary or rescue treatment for BE and EEC. Six abstracts reported aggregated data while two abstracts published individual patient data. All used spray cryotherapy with either liquid nitrogen (N2, n=7 studies) or carbon dioxide (CO2, n=1). Four studies noted failed treatments before cryotherapy with endoscopic mucosal resection being the most common (n=34 cases). All verified histology by biopsy before treatment. There were 8 cases of early squamous cell cancer combined with the majority of cases reporting BE, high grade dysplasia and intramucosal carcinoma. Studies that reported BE length had a mean of 4.4 cm. Cryotherapy was administered over 2-8 cycles for 10-20 seconds per area, with a mean of 4.3 sessions per patient. Overall, 63% of enrolled patients completed treatment. The mean CR was 74% (range: 48-94%). The case series with CO2 cryogen had the highest CR rate (94%). Transient abdominal discomfort was the most common side effect (n=28 cases). Strictures were the most common serious events (n=9 cases), requiring dilation in 4 patients. Conclusion: The current literature suggests that cryotherapy is a safe and effective modality for BE and EEC. Further research using randomized trials is needed to establish efficacy, comparison with other modalities, optimal dosimetry and choice of cryogen (CO2 vs. N2) for better CR rates.